A randomized phase III trial of anthracyclines followed by taxane versus taxane plus carboplatin as (neo)adjuvant therapy in patients with triple-negative breast cancer: KCSG BR 15-1 PEARLY trial.

BACKGROUND

Platinum agents have been shown to increase pathologic complete response (pCR) rates when added to neoadjuvant chemotherapy for triple-negative breast cancer (TNBC). The PEARLY multicenter, randomized, phase III trial investigated the efficacy and safety of adding carboplatin to standard anthracycline-based and taxane chemotherapy for patients with early-stage TNBC in the neoadjuvant or adjuvant settings.

PATIENTS AND

METHODS

Patients with stage II or III TNBC were enrolled. Patients received either standard therapy with doxorubicin and cyclophosphamide followed by a taxane (control arm) or carboplatin in addition to a taxane following doxorubicin and cyclophosphamide (carboplatin arm). The primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival (OS), invasive disease-free survival (IDFS), distant recurrence-free survival (DRFS), pCR rate, and safety.

RESULTS

Between January 2016 and June 2020, 868 patients across 22 institutions in the Republic of Korea were randomly assigned to either the control arm or carboplatin arm. At a median follow-up of 57.2 months, carboplatin significantly improved EFS compared with the control [hazard ratio 0.67, 95% confidence interval (CI) 0.49-0.92, P = 0.012]. The 5-year EFS rates increased from 75.1% to 82.3% with an absolute 7.2% difference. Secondary endpoints, including OS, IDFS, and DRFS, showed directionally consistent trends favoring the carboplatin arm, though none reached statistical significance. Grade 3 or higher treatment-related adverse event rates were more frequent in the carboplatin arm (74.7%) than in the control arm (56.7%), driven primarily by hematologic toxicity.

CONCLUSION

The addition of carboplatin to doxorubicin and cyclophosphamide followed by taxane therapy significantly improved EFS in patients with early-stage TNBC. Despite a higher incidence of grade ≥3 adverse events in the carboplatin arm, no clinically meaningful deterioration in quality of life was observed, supporting a favorable risk-benefit profile for carboplatin incorporation into early TNBC treatment.